Dissection of the Molecular Events Occurring During T Cell Cycle Progression

  • Kendall A. Smith
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 213)


For the first time it has been possible to study the events occurring subsequent to T cell receptor activation with reasonable certainty that the experimental results can be interpreted correctly. We stand at this threshold as a consequence of the identification of the Ti-Tn complex as the receptor for antigen, and the generation of both antagonistic and agonistic monoclonal antibodies reactive with this receptor (1–9). Thus, it has been discerned that activation of T-T3 leads to a rapid (within minutes) increase in intracellular free calcium, and translocation of the calcium-dependent protein kinase (c-kinase) from the cytosol to the membrane (12,13). Subsequently, within a few hours, it is possible to detect transcription of several genes, including those encoding interleukin 2 (IL-2), IL-2 receptors, interferon gamma (IFN-γ) and the c-myc proto-onncogene (14). Moreover, the genes encoding the IL-2 receptor, IFN-γ and c-myc are induced coordinately even in the presence of cycloheximide, thereby suggesting that a simple pre-existing biochemical pathway is responsible for activating these genes (14). However, despite the recognition that activation of both the antigen receptor and the IL-2 receptor are required for T cell proliferation, the precise function of each of these receptors as regards movement of the t cell through the cell cycle has remained obscure. Thus, it has been unclear as to whether activation of the T cell antigen receptor complex promotes movement of the cells through G1 to a point that requires IL-2 just before S-phase, or whether IL-2 itself is responsible for G1 progression.


Chicken Embryo Fibroblast Intracellular Free Calcium Cell Antigen Receptor Cell Receptor Activation Cytoplasmic Free Calcium 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    J. P. Van Wauwe, J. R. DeMey, and J. G. Gossens. A monoclonal anti-human T lymphocyte antibody with potent mitogenic properties. J. Immunol. 124:2708, (1980).Google Scholar
  2. 2.
    T. W. Chang, P. C. Kung, S. P. Gingras, and G. Goldstein. Does OKT3 monoclonal antibody react with an antigen recognition structure on human T cells? Natl. Acad. Sci. USA 78:1805. (1981).ADSCrossRefGoogle Scholar
  3. 3.
    S. C. Meuer, O. Acuto, R. E. Hussey, J. C. Hodgdon, S. F. Schlossman, and E. L. Reinherz. Evidence for the T3-associated 90 k heterodimer as the T cell antigen receptor. Nature 303:808, (1983).ADSCrossRefGoogle Scholar
  4. 4.
    S. C. Meuer, K. A. Fitzgerald, R. E. Hussey, J. C. Hodgdon, S. F. Schlossman, and E. L. Reinherz. Clonotypic structures involved in antigen specific T cell function: relationship to the T3 molecular complex. J. Exp. Med. 157:705, (1983).CrossRefGoogle Scholar
  5. 5.
    S. C. Meuer, J. C. Hodgdon, R. E. Hussey, J. P. Protentis, S. F. Schlossman, and E. L. Reinherz. Antigen-like effects of monoclonal antibodies directed at receptors on human T cell clones. J. Exp. Med. 158:988, (1983).CrossRefGoogle Scholar
  6. 6.
    K. Haskins, R. Kubo, J. White, M. Pigeon, J. Kappler, and P. Marrack. The major histocompatibility complex-restricted antigen receptor on T cells I. Isolation with a monoclonal antibody. J. Exp. Med. 157:1149, (1983).CrossRefGoogle Scholar
  7. 7.
    S. C. Meuer, R. E. Hussey, D. A. Cantrell, J. C. Hodgdon, S. F. Schlossman, K. A. Smith, and E. L. Reinherz. Triggering of the T3-T1 antigen receptor complex results in clonal T cell proliferation through an mterleukin 2 dependent autocrine pathway. Proc. Natl. Acad. Sci. USA 81:1509, (1984)ADSCrossRefGoogle Scholar
  8. 8.
    S. M. Hedrick, D. I. Cohen, E. A. Nielsen, and M. M. Davis. Isolation of cDNA clones encoding T cell-specific membrane-associated proteins. Nature 308:149, (1984).ADSCrossRefGoogle Scholar
  9. 9.
    Y. Chien, D. M. Becker, T. Lindsten, M. Okamura, D. I. Cohen, and M. M. Davis. A third type of murine T cell receptor gene. Nature 312:31, (1984).ADSCrossRefGoogle Scholar
  10. 10.
    A. Weiss, J. Imboden, D. Shoback, and J. Stobo. Role of T3 surface molecules in human T cell activation T3-dependent activation results in an increase in cytoplasmic free calcium. Proc. Natl. Acad. Sci. USA 81:4169, (1984).ADSCrossRefGoogle Scholar
  11. 11.
    M. M. Weiss, J. F. Daley, J. C. Hodgdon, and E. L. Reinherz. Calcium dependency of antigen-specific (T3-T1) and alternative (T11) pathways of human T-cell activation. Proc. Natl. Acad. Sci. USA 81:6836, (1984).ADSCrossRefGoogle Scholar
  12. 12.
    H. F. Oettgen, C. Terhorst, L. C. Cantley, and P. M. Rosoff. Stimulation of the T3-T cell receptor complex induces a membrane-potential sensitive calcium influx. Cell 40:583, (1985).CrossRefGoogle Scholar
  13. 13.
    J. A. Ledbetter, C. H. June, P. J. Martin, C. E. Spooner, J. A. Hansen, and K. E. Meier. Valency of CD3 binding and internalization of the CD3 cell-surface between effects on protein kinase C, cytoplasmic free calcium, and proliferation. J. Immunol. 136:3945, (1986).Google Scholar
  14. 14.
    M. Kronke, W. J. Leonard, J. M. Depper, and W. C. Greene. Sequential expression of genes involved in human T lymphocyte growth and differentiation. J. Exp. Med. 161:1593, (1985).CrossRefGoogle Scholar
  15. 15.
    D. A. Cantrell, and K. A. Smith. Transient expression of interleukin 2 receptors: consequences for T cell growth. J. Exp. Med. 158:1895, (1983).CrossRefGoogle Scholar
  16. 16.
    D. A. Cantrell, and K. A. Smith. The interleukin 2-T cell system: a new cell growth model. Science 224:1312, (1984).ADSCrossRefGoogle Scholar
  17. 17.
    M. Gullberg, and K. A. Smith. The regulation of T cell autocrine growth: T4+ cells become refractory to interleukin 2. J. Exp. Med. 163:270, (1986).CrossRefGoogle Scholar
  18. 18.
    J. S. Stern, and K. A. Smith. Interleukin 2 induction of T cell G1 progression and c-myb expression. Science (in press).Google Scholar
  19. 19.
    A. L. Maizel, S. R. Mehta, S. Häuft, D. Franzini, L. B. Lachman, and R. J. Ford. Human T lymphocyte/monocyte interaction in response to lectin: kinetics of entry into the s-phase. J. Immunol. 127:1058, (1981).Google Scholar
  20. 20.
    K. A. Smith, and D. A. Cantrell. Interleukin 2 regulates its won receptors. Proc. Natl. Acad. Sci. USA 82:864, (1985).ADSCrossRefGoogle Scholar
  21. 21.
    K. A. Smith. Regulation of T cell proliferation: role of T cell antigen receptors versus interleukin 2 receptors. In Host resistance to Infectious Agents, Tumors, and Allografts, The Rockefeller Press, New York, (1986) pp30.Google Scholar
  22. 22.
    T. J. Gonda, D. K. Sheiness, and J. M. Bishop. Transcripts from the cellular homologs of retroviral oncogenes — distribution among chicken tissues. Molec. Cell. Biol. 2:617, (1982).Google Scholar
  23. 23.
    C. B. Thompson, P. B. Challoner, P. E. Neiman, and M. Groudine. Expression of the c-myb proto-oncogene during cellular proliferation. Nature 319:374, (1986).ADSCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1987

Authors and Affiliations

  • Kendall A. Smith
    • 1
  1. 1.The Department of MedicineDartmouth Medical SchoolHanoverUSA

Personalised recommendations